Publications by authors named "A N Kettenbach"
Microglia respond to cytotoxic protein aggregates associated with the progression of neurodegenerative disease. Pathological protein aggregates activate the microglial NLRP3 inflammasome resulting in proinflammatory signaling, secretion, and potentially pyroptotic cell death. We characterized mixed sex primary mouse microglia exposed to microbial stressors and alpha synuclein preformed fibrils (αsyn PFFs) to identify cellular mechanisms related to Parkinson's disease.
View Article and Find Full Text PDFDespite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease.
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- Triple-negative breast cancer (TNBC) is a highly aggressive subtype with varied characteristics, limited treatment choices, and poor clinical outcomes, particularly when associated with homologous recombination deficiency (HRD).
- The study analyzed TNBC tumors from two groups (n=32 and n=58), revealing significant differences in genome-wide copy number and methylation alterations linked to HRD, including lower methylation in specific genomic regions.
- Findings indicate that HRD in TNBC is associated with key biological pathways, and using machine learning can aid in classifying tumors based on HRD and methylation patterns, offering potential for improved treatment strategies.
Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA polymerase II (RNA Pol II) and associated factors to control transitions between these steps and to act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, although their roles remain less well understood.
View Article and Find Full Text PDFProtein Ser/Thr phosphatase PP1 is always associated with one or two regulatory subunits or RIPPOs. One of the earliest evolved RIPPOs is PPP1R2, also known as Inhibitor-2. Since its discovery nearly 5 decades ago, PPP1R2 has been variously described as an inhibitor, activator or (metal) chaperone of PP1, but it is still unknown how PPP1R2 affects the function of PP1 in intact cells.
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